P1192: ANTI-PD-1 ANTIBODY (TISLELIZUMAB) COMBINED WITH R-CHOP FOR THE TREATMENT OF PREVIOUSLY UNTREATED PRIMARY MEDIASTINAL B-CELL LYMPHOMA: A PROSPENTIVE PHASE II STUDY
Authors: Wu Mei, Zhu Lin, LI Shan, Tu Erde Jia Erbao, Wang Shanshan, Liang Xiao, Hu Xin, Guo LI, A Dili Abulikemujiang, Maimaitirexiati Xianmusiya, Ren Ruirui, Wen Shujuan
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma of thymic origin. Due to the low incidence rate of PMBCL, there is currently no internationally accepted standard first-line treatment regimen. Dose-adjusted (DA) EPOCH-R which is the more commonly used first-line therapy plan is not so effective because patients usually cannot tolerate it. The R-CHOP regimen is comparable to the R-DA-EPOCH for the first-line treatment of PMBCL in terms of survival and has a better safety profile l,2. Meanwhile, patients with PMBCL usually have alterations of 9p24.1, leading to overexpression of PDL-1/2. Previous studies have found that PD-1 monoclonal antibody shows good efficacy in recurrent and refractory PMBCL3,4. Tislelizumab, a humanized IgG4 antibody that binds PD-1 with high affinity, minimizes binding to Fcγ receptor 1 (FcγRI) on macrophages by the genetic engineering of Fc segment, abrogating antibody-dependent phagocytosis (ADCP)–induced T-cell clearance. The efficacy and safety of its combination with R-CHOP in previously untreated PMBCL is not yet clear. We speculate that the combination of both may be a new option for the first-line therapy for PMBCL patients with good efficacy and low toxicity. Aims: To explore the efficacy and safety of the combination therapy of Tislelizumab and R-CHOP on the previously untreated PMBCL patients, and to perform exploratory analysis of treatment-related biomarkers. Methods: This is a single-arm, multi-center, phase II clinical study (ChiCTR2100044313). Patients aged 18 years or older with a diagnosis of PMBCL and previously untreated were eligible. Eligible patients received 6 cycles of Tislelizumab (200 mg D1), Rituximab (375 mg/m2 D1), Cyclophosphamide (750 mg/m2 D2), Pirarubicin (50 mg/m2 D2), Vincristine (1.4 mg/m2, maximum dose 2 mg, D2), Prednisone (100 mg/d D2-6), every 21 days for 1 cycle. Disease response assessments were performed by positron emission tomography and computed tomography (PET-CT) or enhanced CT every two cycles, meanwhile peripheral blood ctDNA was monitored, and treatment-related adverse effects were assessed and recorded. The primary endpoint was objective remission rate (ORR). The secondary endpoints included treatment safety, progression-free survival (PFS) and overall survival (OS), and the exploratory analyses of the correlation between PD-L1 expression in tumor tissues, tumor-associated macrophages (TAM) phenotype in tumor microenvironment and efficacy. Results: From June 2020 to December 2022, 8 patients were enrolled with the median age of 33 years, 2 male and 6 female, all patients had large mediastinal mass at initial diagnosis. 6 patients had PD-L1 expression (VENTANA SP263) above 80%, and 2 cases could not be further tested due to insufficient tissue specimens. The ORR was 100%, and the CR rate was 87.5% (7/8) after 6 cycles of treatment. 1(the 5th) patient reached PR after 6 cycles of treatment due to irregular hospitalization, and CR was achieved after another 2 cycles of regular treatment. 4 patients underwent ctDNA test, and the PET-CT and ctDNA assessments were negative in three patients at the end of treatment, and the 5th patient achieved PR on PET-CT, but the ctDNA assessment was negative. The most common adverse events (AEs) were gastrointestinal reactions, 2 patients experienced grade IV myelosuppression and 1 patient had grade I hyperthyroidism. No treatment-related deaths occurred. Summary/Conclusion: Tislelizumab combined with R-CHOP for the treatment of previously untreated PMBCL had good efficacy and sustained response with low toxicity. Longer follow-up is required to access the survival benefit of this regimen. Figure 1: Disease Remission in the Included PatientsKeywords: Immune therapy, Chemotherapy, B cell lymphoma